Name: a free-breathing fmri method to study human olfactory function
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以下实验方案遵循宾夕法尼亚州立大学医学院机构审查委员会的指导方针，人体受试者在参加研究之前给予书面知情同意书。 注意:为了演示的目的，提出了一种使用市售的MRI兼容嗅觉计的简单气味刺激范例。已经证明这一范例有效降低了习惯效应，并产生了可靠的嗅觉功能磁共振成像数据15 。本协议中概述的某些步骤可能特定于使用的嗅觉仪的类型。然而，可以以类似的方式使用任何类型的具有类似能力的家用或可商购的设备。嗅觉仪必须能够监测呼吸，以及提供精确定时的气味剂序列。确保整个气味递送系统（包括嗅觉测量仪）采用对气味化学物质（ 如玻璃和聚四氟乙烯）无惰性的物质构成，气味通道光滑，气密，死区最小。 范式设计<ol><li>通过在可编程嗅觉计上指定气流顺序来创建新的范例。 注意:阀门序列是保持不同浓度或类型气味剂的特定空气通道的打开和关闭的顺序和时间。在这个示范中，六个通道的每个阀门打开两次，共十二个气味输送。每当一个阀门打开时，所有其他阀门关闭，并且只有在所有其他阀门已经打开一次后，每个阀门再次打开。 <ol><li>分配刺激的持续时间（特定通道的打开）以及要关闭通道的持续时间。 注意:在本示范中，气味呈现的持续时间为6秒，而通道关闭的持续时间从22秒变化到38秒。 </li><li>设置阀门打开和关闭顺序的重复次数。这里重复次数为1次。 </li><li>以相同的流速交替显示每种气味呈现，呈现无臭的空气。例如，在50％相对湿度和22°C的室温下，以6L / min的流速将气流传送到具有或没有气味的对象。 注意:这很重要，因为气流的变化可能会引起触觉。 </li></ol></li></ol> 2.气味准备<ol><li>通过考虑气味价格，愉悦度，强度，熟悉度和三叉分量来选择适合气味刺激范例的气味剂（ 见表1 ）。 注意: 表1列出了一些常用的气味剂。选择薰衣草气味用于此示范，因为它在低至中等程度上具有最小的三叉神经刺激浓度通常被认为是愉快和熟悉的。 </li><li>选择合适的溶剂（ 例如 ，水，矿物油，1,2-丙二醇，乙醇）中以制备臭气物质的解决方案。 注意:这里，使用1,2-丙二醇作为加臭剂溶液的溶剂。 </li><li>为气味刺激范式选择合适的气味浓度。例如，稀释的薰衣草油在1,2-丙二醇中的浓度为0.10％（体积/体积），用于嗅觉刺激19 。 注意:这可以通过一组正常受试者对一系列不同浓度的心理物理学评估来完成。 </li><li>将适当的气味溶液放入加味剂容器中。确保所有容器具有相同的空间，相同量的溶液和溶液的相同表面积。例如，使用六个300毫升尺寸的玻璃瓶作为加臭剂容器，每个瓶子保持50毫升0.10％的薰衣草油溶液。 </li><li>连接一个将气味容器放入适当的通道进行气味输送。 </li></ol>嗅觉仪设置<ol><li>检查连接是否确保所有加臭剂容器均正确连接到加味剂载体上。不要过紧，因为这可能会损坏密封。通过检查通过每个加臭剂容器的气流，在后续步骤中确保适当的密封性。 </li><li>将气味载体放置在磁体室中，并将每个管连接到室外的嗅觉计，因为主机不兼容MR。目视检查管道中的任何扭结，因为这将影响气流。将在以后的步骤中检查每个通道的气流。 </li><li>通过将数字与正确的端口相匹配，将所有管从嗅觉仪安全地连接到加味剂载体。为了准确性，对管进行颜色编码，使得通道1的粉红色，通道2的蓝色等 。 </li><li>确保通过所有通道的气流通过连接流动是一致的米到管道的输出端。手动打开嗅觉仪控制面板上的每个通道，调整每个通道和冲洗管线的总空气流量以及流量，直到每个通道的流量一致。 </li><li>用聚四氟乙烯（PTFE）管将面罩或鼻片连接到加味剂载体上。当切换通道时，确保传送到被摄体的气流（ 例如 6 L / min）一致。 </li><li>将射频触发从MRI系统连接到嗅觉仪上的"触发"端口，以同步气味刺激范式和fMRI图像采集。可能需要光电信号转换器。 </li><li>将每个通道和冲洗管线的总空气流量和流量调整到设计量。例如，6L / min的总空气流量和每个通道和冲洗管线的流量为3L / min。 </li><li>连接气动呼吸系统r带通过气动电信号转换器盒到嗅觉计的响应端口。 </li><li>如果需要主观响应，请通过气动电气信号转换箱将气动响应垫连接到嗅觉计的响应端口。 </li></ol> 4.实验程序<ol><li>进行预筛选，以确保MRI程序对于受试者是安全的。 <ol><li>询问病史，包括潜在的种植体，幽闭恐惧症或其他可能干扰受试者安全参与功能磁共振成像研究的能力的预先存在的病症。另外，进行气味的气味阈值测试，以确保受试者在实验过程中可闻到气味。 </li></ol></li><li>使患者仰卧在MRI检查床上。将面罩或鼻片妥善放置在受试者身上，以确保空气吹入鼻孔。将呼吸传感器放在t上他的胸部或腹部。要求受试者正常呼吸。根据嗅觉计显示屏上看到的呼吸模式手动调节保持呼吸传感器的皮带的紧度和位置。 </li><li>创建一个数据文件夹来记录嗅觉计数器中的呼吸数据。单击"文件管理器"，输入分配给当前主题的主题ID，然后"确认"输入。 </li><li>使用"范例检查"选项来测试异味递送和吸入的同步，而不需要刺激输送，如果需要，可以手动调整"气门延迟"时间，以确保气味传播的开始与受试者的吸入阶段同步。 </li><li>通过在嗅觉计的控制单元上选择"触发"模式，设置气味刺激和fMRI图像采集之间的同步。 注意:这允许气味刺激范例从外部触发开始，通过";触发"源自MRI系统的端口。因此，在接收到来自扫描仪的外部触发之前，范例将不会运行。请注意MRI扫描仪发出什么样的触发脉冲（电或光）。可能需要信号转换器来链接这两个系统。 </li><li>通过在嗅觉计的控制单元上选择"resp trigger start"来激活呼吸触发。 注意:激活时，每个范例序列元素的开始与吸入同步。这可以通过从呼气阶段开始延迟大约呼吸周期的一半的气味来经验地实现。 </li><li>在MRI控制台上启动fMRI图像采集;一旦图像采集开始，气味刺激范式就会开始。监测任何不规则呼吸活动的呼吸模式。 注意:不规则的呼吸活动可能是高原，更长和更长周期的形式，或波涛汹涌这里，使用BOLD信号敏感的T 2 *加权回波平面成像序列用于具有2,000ms重复时间，30ms回波时间，90°翻转角，220mm×220mm视野的fMRI图像采集，80 ×80采集矩阵，30 4 mm厚轴向切片，加速因子为2，用于集成并行成像技术。 </li><li>完成成像协议后，将物体从磁铁上移开，然后取下面罩/鼻片。 </li></ol>嗅觉清洁<ol><li>关闭空气泵。将加味剂容器从气味载体中分离出来，并用干净的空的容器代替。 </li><li>打开气泵。用无味的空气冲洗每个通道5分钟，以除去空气管线中的残留气味物质。 </li><li>关闭嗅觉仪。 </li><li>用酒精擦拭液消毒鼻子或面罩。用温水冲洗面罩或鼻子，然后风干。 </li></ol&gt; 数据分析<ol><li>要处理数据，将呼吸数据文件加载到开源软件嗅觉网络刺激编辑工具（ONSET）（www.pennstatehershey.org/web/nmrlab/resources/software/onset） 15 注意:ONSET软件是由孙晓宇开发的。将自动检测基于范式和呼吸痕迹时间的气味刺激开始。实际刺激矢量被定义为气味递送期间每次有效吸入的开始时间。 <ol><li>测量和比较气味和无味周期之间的呼吸速率和体积（每个吸入和呼出相位下的面积） 15 。 注意:这些呼吸参数在气味和无味期间间无显着差异。 </li><li>使用来自ONSET的实际起始和持续时间向量处理fMRI数据以激活中心olfac系统15 。 </li></ol></li></ol>

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	<li>Doty, R. L., Reyes, P. F., Gregor, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Presence+of+both+odor+identification+and+detection+deficits+in+Alzheimer's+disease.">Presence of both odor identification and detection deficits in Alzheimer's disease.</a> Brain Res Bull. 18 (5), 597-600 (1987).</li><li>Hummel, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Olfactory+FMRI+in+patients+with+Parkinson's+disease.">Olfactory FMRI in patients with Parkinson's disease.</a> Front Integr Neurosci. 4, 125 (2010).</li><li>Mesholam, R. I., Moberg, P. J., Mahr, R. N., Doty, R. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Olfaction+in+neurodegenerative+disease:+a+meta-analysis+of+olfactory+functioning+in+Alzheimer's+and+Parkinson's+diseases.">Olfaction in neurodegenerative disease: a meta-analysis of olfactory functioning in Alzheimer's and Parkinson's diseases.</a> Arch Neurol. 55 (1), 84-90 (1998).</li><li>Pause, B. M., Miranda, A., G&#246;der, R., Aldenhoff, J. B., Ferstl, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reduced+olfactory+performance+in+patients+with+major+depression.">Reduced olfactory performance in patients with major depression.</a> J Psychiatr Res. 35 (5), 271-277 (2001).</li><li>Vasterling, J. J., Brailey, K., Sutker, P. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Olfactory+identification+in+combat-related+posttraumatic+stress+disorder.">Olfactory identification in combat-related posttraumatic stress disorder.</a> J Trauma Stress. 13 (2), 241-253 (2000).</li><li>Anderson, A. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dissociated+neural+representations+of+intensity+and+valence+in+human+olfaction.">Dissociated neural representations of intensity and valence in human olfaction.</a> Nat Neurosci. 6 (2), 196-202 (2003).</li><li>Gottfried, J. A., Deichmann, R., Winston, J. S., Dolan, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+heterogeneity+in+human+olfactory+cortex:+an+event-related+functional+magnetic+resonance+imaging+study.">Functional heterogeneity in human olfactory cortex: an event-related functional magnetic resonance imaging study.</a> J Neurosci. 22 (24), 10819-10828 (2002).</li><li>Sobel, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sniffing+and+smelling:+separate+subsystems+in+the+human+olfactory+cortex.">Sniffing and smelling: separate subsystems in the human olfactory cortex.</a> Nature. 392 (6673), 282-286 (1998).</li><li>Sun, X., Wang, J., Weitekamp, C. W., Yang, Q. X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Novel+Data+Processing+Method+for+Olfactory+fMRI+Examinations.">A Novel Data Processing Method for Olfactory fMRI Examinations.</a> Proc Intl Soc Mag Res Med. 18 (2010), 1161 (2010).</li><li>Zatorre, R. J., Jones-Gotman, M., Evans, A. C., Meyer, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+localization+and+lateralization+of+human+olfactory+cortex.">Functional localization and lateralization of human olfactory cortex.</a> Nature. 360 (6402), 339-340 (1992).</li><li>Boley, J. C., Pontier, J. P., Smith, S., Fulbright, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Facial+changes+in+extraction+and+nonextraction+patients.">Facial changes in extraction and nonextraction patients.</a> Angle Orthod. 68 (6), 539-546 (1998).</li><li>Furman, J. M., Koizuka, I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reorientation+of+poststimulus+nystagmus+in+tilted+humans.">Reorientation of poststimulus nystagmus in tilted humans.</a> J Vestib Res. 4 (6), 421-428 (1994).</li><li>Loevner, L. A., Yousem, D. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Overlooked+metastatic+lesions+of+the+occipital+condyle:+a+missed+case+treasure+trove.">Overlooked metastatic lesions of the occipital condyle: a missed case treasure trove.</a> Radiographics. 17 (5), 1111-1121 (1997).</li><li>Tabert, M. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Validation+and+optimization+of+statistical+approaches+for+modeling+odorant-induced+fMRI+signal+changes+in+olfactory-related+brain+areas.">Validation and optimization of statistical approaches for modeling odorant-induced fMRI signal changes in olfactory-related brain areas.</a> Neuroimage. 34 (4), 1375-1390 (2007).</li><li>Wang, J., Sun, X., Yang, Q. X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Methods+for+olfactory+fMRI+studies:+Implication+of+respiration.">Methods for olfactory fMRI studies: Implication of respiration.</a> Hum Brain Mapp. 35 (8), 3616-3624 (2014).</li><li>Gottfried, J. A., O'Doherty, J., Dolan, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Appetitive+and+aversive+olfactory+learning+in+humans+studied+using+event-related+functional+magnetic+resonance+imaging.">Appetitive and aversive olfactory learning in humans studied using event-related functional magnetic resonance imaging.</a> J Neurosci. 22 (24), 10829-10837 (2002).</li><li>Popp, R., Sommer, M., M&#252;ller, J., Hajak, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Olfactometry+in+fMRI+studies:+odor+presentation+using+nasal+continuous+positive+airway+pressure.">Olfactometry in fMRI studies: odor presentation using nasal continuous positive airway pressure.</a> Acta Neurobiol Exp (Wars). 64 (2), 171-176 (2004).</li><li>Wang, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Olfactory+Habituation+in+the+Human+Brain.">Olfactory Habituation in the Human Brain.</a> Proc Intl Soc Mag Res Med. 20, 2150 (2012).</li><li>Grunfeld, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+responsiveness+of+fMRI+signal+to+odor+concentration).">The responsiveness of fMRI signal to odor concentration).</a> , A237-A238 (2005).</li><li>Jia, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+MRI+of+the+olfactory+system+in+conscious+dogs.">Functional MRI of the olfactory system in conscious dogs.</a> PLoS One. 9 (1), e86362 (2014).</li><li>Karunanayaka, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Networks+involved+in+olfaction+and+their+dynamics+using+independent+component+analysis+and+unified+structural+equation+modeling.">Networks involved in olfaction and their dynamics using independent component analysis and unified structural equation modeling.</a> Hum Brain Mapp. 35 (5), 2055-2072 (2014).</li><li>Royet, J. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+neuroanatomy+of+different+olfactory+judgments.">Functional neuroanatomy of different olfactory judgments.</a> Neuroimage. 13 (3), 506-519 (2001).</li><li>Doty, R. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Influence+of+age+and+age-related+diseases+on+olfactory+function.">Influence of age and age-related diseases on olfactory function.</a> Ann N Y Acad Sci. 561, 76-86 (1989).</li><li>Wang, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Olfactory+deficit+detected+by+fMRI+in+early+Alzheimer's+disease.">Olfactory deficit detected by fMRI in early Alzheimer's disease.</a> Brain Res. 1357, 184-194 (2010).</li><li>Moessnang, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Altered+activation+patterns+within+the+olfactory+network+in+Parkinson's+disease.">Altered activation patterns within the olfactory network in Parkinson's disease.</a> Cereb Cortex. 21 (6), 1246-1253 (2011).</li><li>Vasavada, M. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Olfactory+cortex+degeneration+in+Alzheimer's+disease+and+mild+cognitive+impairment.">Olfactory cortex degeneration in Alzheimer's disease and mild cognitive impairment.</a> J Alzheimers Dis. 45 (3), 947-958 (2015).</li><li>Jacobs, H. I., Radua, J., L&#252;ckmann, H. C., Sack, A. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Meta-analysis+of+functional+network+alterations+in+Alzheimer's+disease:+toward+a+network+biomarker.">Meta-analysis of functional network alterations in Alzheimer's disease: toward a network biomarker.</a> Neurosci Biobehav Rev. 37 (5), 753-765 (2013).</li><li>Murphy, C., Cerf-Ducastel, B., Calhoun-Haney, R., Gilbert, P. E., Ferdon, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=ERP,+fMRI+and+functional+connectivity+studies+of+brain+response+to+odor+in+normal+aging+and+Alzheimer's+disease.">ERP, fMRI and functional connectivity studies of brain response to odor in normal aging and Alzheimer's disease.</a> Chem Senses. 30 Suppl 1, i170-i171 (2005).</li><li>Hummel, T., Kobal, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differences+in+human+evoked+potentials+related+to+olfactory+or+trigeminal+chemosensory+activation.">Differences in human evoked potentials related to olfactory or trigeminal chemosensory activation.</a> Electroen Clin Neuro. 84 (1), 84-89 (1992).</li><li>Cerf-Ducastel, B., Murphy, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=FMRI+brain+activation+in+response+to+odors+is+reduced+in+primary+olfactory+areas+of+elderly+subjects.">FMRI brain activation in response to odors is reduced in primary olfactory areas of elderly subjects.</a> Brain Res. 986 (1-2), 39-53 (2003).</li><li>Cain, W. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Contribution+of+the+trigeminal+nerve+to+perceived+odor+magnitude.">Contribution of the trigeminal nerve to perceived odor magnitude.</a> Ann NY Acad Sci. 237, 28-34 (1974).</li><li>Murphy, C., Gilmore, M. M., Seery, C. S., Salmon, D. P., Lasker, B. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Olfactory+thresholds+are+associated+with+degree+of+dementia+in+Alzheimer's+disease.">Olfactory thresholds are associated with degree of dementia in Alzheimer's disease.</a> Neurobiol Aging. 11 (4), 465-469 (1990).</li><li>Doty, R. L., Brugger, W. E., Jurs, P. C., Orndoff, M. A., Snyder, P. J., Lowry, L. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intranasal+trigeminal+stimulation+from+odorous+volatiles:+Psychometric+responses+from+anosmic+and+normal+humans.">Intranasal trigeminal stimulation from odorous volatiles: Psychometric responses from anosmic and normal humans.</a> Physiol Behav. 20 (2), 175-185 (1978).</li><li>Kobal, G., Hummel, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Olfactory+and+intranasal+trigeminal+event-related+potentials+in+anosmic+patients.">Olfactory and intranasal trigeminal event-related potentials in anosmic patients.</a> Laryngoscope. 108 (7), 1033-1035 (1998).</li><li>Frasnelli, J., Lundstr&#246;m, J. N., Sch&#246;pf, V., Negoias, S., Hummel, T., Lepore, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dual+processing+streams+in+chemosensory+perception.">Dual processing streams in chemosensory perception.</a> Front Hum Neurosci. 6, (2012).</li><li>Yousem, D. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gender+effects+on+odor-stimulated+functional+magnetic+resonance+imaging.">Gender effects on odor-stimulated functional magnetic resonance imaging.</a> Brain Res. 818 (2), 480-487 (1999).</li><li>Koulivand, P. H., Ghadiri, M. K., Gorji, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lavender+and+the+nervous+system.">Lavender and the nervous system.</a> Evid Based Compl Alt Med. 2013, (2013).</li><li>Yousem, D. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+MR+imaging+during+odor+stimulation:+Preliminary+data.">Functional MR imaging during odor stimulation: Preliminary data.</a> Neuroradiology. 204 (3), 833-838 (1997).</li><li>Hummel, T., Doty, R. L., Yousem, D. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+MRI+of+intranasal+chemosensory+trigeminal+activation.">Functional MRI of intranasal chemosensory trigeminal activation.</a> Chem Senses. 30 (suppl. 1), i205-i206 (2005).</li></ol>

作者没有什么可以披露的。

应仔细考虑实验程序，并妥善执行收集可靠的嗅觉激活数据。协议中的关键步骤包括实施呼吸引发的范例，使气味传递与图像采集同步，制备适当浓度的气味来控制心理物理反应，用可靠稳定的呼吸信号和恒定气流设置嗅觉仪，以及后处理呼吸和使用ONSET的气味施用定时数据追溯调整气味发起向量。在设计范例和分析数据时，需要考虑诸如习惯，心理物理反应和呼吸模式等混淆因素。当受试者暴露于长时间的气味时，主要嗅皮质的激活在接触的几秒钟内降低，这使得有必要利用具有简短施用顺序的事件相关范例的气味剂。嗅觉也应该密切监测，因为它可以诱发梨形皮质的激活，甚至没有气味8 。最重要的是，呼吸是一个主要的混杂变量，如果它不与加味剂管理同步。我们已经表明，吸入和气味发作与呼吸触发范式的同步产生更可靠的活化15 。 自由呼吸fMRI方法最常见的问题是气味传播和吸入事件之间的差异同步，这可能是由实验设置中的三个缺陷引起的。首先，最常见的呼吸传感器设置不正确。当胸带过紧时，呼吸信号将会平稳，导致同​​步不良。第二，"阀门延迟"时间校准不佳，这可能导致呼吸过程中气味传递太早或太晚CLE。第三，"阀门延迟"时间校准后，受试者的呼吸模式不一致。因此，对于受试者正常地在磁体中呼吸的预扫描训练以及在fMRI扫描过程中呼吸模式的密切监测是重要的。 当选择气味剂用于研究时，考虑强度，价态和三叉神经刺激是重要的，因为这些变量可导致不同类型的心理物理反应和相关的功能磁共振成像激活。例如，弱的强度可能引起嗅觉的倾向，而强烈的强度可能导致不自主的呼吸或更快的习惯。气味强度也显示与大脑激活相关20 。一个替代范例由四种浓度的薰衣草组成，在整个实验中呈现强度增加的趋势，有效降低了习惯21 。一个odora的价nt还激活大脑的不同区域，必须考虑到数据解释22 。例如，一项研究通过气味价16表示不同的时间特征。另外，许多气味剂具有不同程度的三叉神经刺激，这应该被考虑。 重要的是要认识到，这种自由呼吸的范例不一定适用于所有嗅觉功能磁共振成像研究。它仅提供了对嗅觉功能磁共振成像研究很重要的特殊考虑的一个例子。同样重要的是要注意，本报告中所展示的实验程序并不是所用嗅觉仪所特有的。该设备可以用具有相似能力的任何嗅觉仪器代替。例如，嗅觉仪必须具有呼吸监测能力，以及执行具有多种气味源的呼吸触发范式的能力。 Additionally，虽然这个实验是使用薰衣草提出的，但其他气味剂可能被研究者所取代，尽管重要的是尽量减少诸如三叉神经刺激和气味浓度之类的混杂变量。 这种自由呼吸的功能磁共振成像方法旨在消除中心嗅觉系统的预处理，并减少气味刺激重复事件之间的不一致。中心嗅觉系统的预处理可能因受试者而异，这可能导致原发嗅觉结构中的活化变化。重复事件的一致性， 例如气味刺激以触发中枢嗅觉系统的激活，对于成功执行事件相关的fMRI协议是至关重要的。此外，通过自由呼吸技术，在执行嗅觉功能磁共振成像模式期间，对于受试者不能提供任何提示或任务。因为它在功能方面需要最少的努力数据采集​​，它可以成为研究一些流行的神经退行性疾病和疾病， 如阿尔茨海默病的嗅觉缺陷的有价值的工具。 最近的研究已经使用嗅觉功能磁共振成像来探索神经变性疾病中的脑激活模式。在神经变性疾病，特别是阿尔茨海默氏病和帕金森氏病的嗅觉障碍，包括与气味检测，识别，和识别3,23困难。然而，虽然嗅觉障碍是发病的早期阶段明显指标，嗅觉功能丧失往往被忽视或者是由于正常的年龄相关的下降1，23。因此，进一步探索与这些疾病中的嗅觉功能障碍相关的不同活化模式，以更好地诊断t是非常重要的早起。在阿尔茨海默氏病，活化图案显著在初级嗅皮质，以及海马和岛相对于健康，年龄匹配的对照24时减小。此外，研究人员发现，在帕金森氏症患者，杏仁核和丘脑显示出高于健康对照组少活化，而较高的激活是地区所看到的，如与对照组相比2左额下回。另外的研究表明帕金森氏病患者的梨状和眶额叶皮质中的超活化25 。这种不同的激活模式似乎超越了结构病理学，从而证明了功能数据采集在理解和诊断神经变性疾病中的重要性，并且需要创新嗅觉功能磁共振成像的准确性和灵敏度。 因此，进一步的stu在人类嗅觉系统死亡与fMRI可能有潜力开发生物标志物用于神经退行性疾病的早期诊断。事实上，研究已经取得进展，包括灵敏度的示范正常老化和老年痴呆症患者24，26之间的激活水平。一个这样的研究表明，神经网络的破坏是常常可检测的认知缺陷中某些神经变性疾病27展示自己甚至之前。这进一步突出了嗅觉功能障碍调查作为早期诊断这种疾病的潜在工具的重要性。证据也表明阿尔茨海默氏病的大规模嗅觉网络处理变化存在，除了特定嗅觉区域的变化外，还强调进一步探索嗅觉功能连通性28的重要性。桑斯嗅觉激活水平作为生物标志物的灵敏度取决于对气味刺激的敏感性和实验重现性，这突出了嗅觉系统映射的可靠性的重要性。综合起来，本文提供的例子提供了嗅觉功能磁共振成像可以有效地用于了解中枢嗅觉系统的复杂性和理解的临床重要性的一瞥。

人类嗅觉系统被认为远远超过感觉系统，因为嗅觉也在稳态调节和情绪中起重要作用。临床上，人的嗅觉系统已知是易受许多流行的神经疾病和精神疾病，如阿尔茨海默氏病，帕金森氏病，创伤后应激障碍和抑郁症1，2，3，4，5的攻击。目前，具有血氧水平依赖性（BOLD）对比度的功能磁共振成像（fMRI）是映射人脑功能的最有价值的技术。已经获得了关于中心嗅觉结构（ 例如梨状皮层，眶额叶皮质，杏仁核和岛状皮层）的特定功能的大量知识神游6，7，8，9，10。 然而，fMRI在人类中枢嗅觉系统及相关疾病研究中的应用受到两个主要障碍的阻碍:BOLD信号的快速习惯和呼吸可变调制。在日常生活中，当一段时间暴露于气味时，我们很快就习惯了香味。事实上，使用嗅觉功能磁共振成像研究的情况下，气味引起的磁共振成像信号迅速被习惯化，这对上刺激范例设计8，10，11，12，13，14是一个挑战衰减。原始嗅皮层初始显着的BOLD信号仅持续存在在发臭后几秒钟。因此，嗅觉fMRI范例应避免在短时间内长时间或频繁的气味刺激。为了减少习惯效应，一些研究试图在fMRI范式中呈现交替气味。然而，这种方法可能使数据分析复杂化，因为每种气味剂都可以被视为独立的刺激事件。 另一个技术问题出现在受试者呼吸模式的变异性;在固定时间范式下，吸入并不总是与加臭剂给药同步。嗅觉刺激的发作和持续时间由每个人的呼吸调节，这混淆了fMRI数据质量和分析。一些研究尝试通过视觉或听觉线索来缓解这个问题，以使呼吸和气味发作同步，但受试者的依从性是可变的，特别是在临床人群中。大脑激活相关联在某些应用中，这些线索也可能使数据分析复杂化。因此，同步吸入与气味输送对于嗅觉功能磁共振成像研究至关重要15 。 对嗅觉功能磁共振成像，特别是在数据分析过程中至关重要的另外一个考虑因素是气味选择。相对于感知强度找到合适的加味剂浓度对于在各种实验条件或疾病下的大脑中的活化水平的定量和比较是重要的。气味选择还必须考虑到气味价格或愉悦度。这就是所谓的嗅觉学习16，17，以引起不同时间轮廓。为此，选择薰衣草气味进行部分验证。根据具体研究的目的，不同的气味剂可能是更好的选择。此外，三叉神经刺激必须最小化以减少e激活与嗅觉没有直接关系18 。 在本报告中，我们展示了在磁共振环境中使用嗅觉仪设置和运行呼吸触发范式的fMRI技术。我们还提供一个后处理工具，可以减少在数据采集期间可能发生的一些时序错误，以进一步改进数据分析。

<table><tbody><tr><td>3T MR scanner</td><td>Siemens</td><td></td><td>Any MR scanner is acceptable.&amp;nbsp;</td></tr><tr><td>Olfactometer</td><td>Emerging Tech Trans, LLC</td><td></td><td>Any olfactometer with similar capabilities is acceptable.</td></tr><tr><td>6-channel odorant carrier</td><td>Emerging Tech Trans, LLC</td><td></td><td></td></tr><tr><td>Nosepiece/applicator</td><td>Emerging Tech Trans, LLC</td><td></td><td></td></tr><tr><td>PTFE tubing</td><td>Emerging Tech Trans, LLC</td><td></td><td></td></tr><tr><td>TTL convertor box</td><td>Emerging Tech Trans, LLC</td><td></td><td></td></tr><tr><td>Respiratory sensor belt</td><td>Emerging Tech Trans, LLC</td><td></td><td></td></tr><tr><td>Lavender oil</td><td>Givaudan Flavors Corporation</td><td></td><td></td></tr><tr><td>1,2 propanediol</td><td>Sigma</td><td>P6209</td><td></td></tr><tr><td>ONSET</td><td></td><td></td><td>www.pennstatehershey.org/web/nmrlab/resources/software/onset</td></tr><tr><td>SPM8&amp;nbsp;</td><td>Wellcome Trust Center for Neuroimaging, University College London, London, UK&amp;nbsp;</td><td></td><td></td></tr></tbody></table>

a free-breathing fmri method to study human olfactory function

人类嗅觉的研究是一个非常复杂和有价值的领域，应用范围从生物医学研究到临床评估。目前，功能磁共振成像（fMRI）的人体中枢嗅觉系统的功能评估仍然是一个挑战，因为有几个技术难点。在考虑使用fMRI映射中心嗅觉系统的功能的有效方法时，需要考虑一些重要的变量，包括适当的气味选择，气味呈现和呼吸之间的相互作用以及对气味剂的潜在预期或习惯。与事件相关的呼吸引发的嗅觉功能磁共振成像技术可以精确地管理气味，以刺激嗅觉系统，同时最大限度地减少潜在的干扰。使用我们的数据后处理方法，可以有效地捕获原始嗅觉皮质中fMRI信号的精确定位。技术前这里提供了一种有效和实用的方法来产生可靠的嗅觉功能磁共振成像。随着我们开始进一步了解人类嗅觉系统的复杂性，这种技术最终可以应用于临床领域，作为与嗅觉退化有关的疾病的诊断工具，包括阿尔茨海默病和帕金森病。

图1显示了考虑MR兼容性的磁体室内外的嗅觉功能磁共振成像的设置。 图2a示出了标准固定时间范例，而图2b展示了一个范例，其中"呼吸触发"允许气味输送和吸入的同步。 具有清晰吸入峰值的常规呼吸模式对于实施准确的呼吸触发范式至关重要。因此，呼吸传感器的调整是实验设置中的重要一步。 图3显示了呼吸传感器设置不正确（ 图3a ）和正确（ 图3b ）时的样品呼吸痕迹。如果呼吸嗅觉模式不规则或呼吸信号平稳，嗅觉仪将无法准确确定呼吸模式，并且气味呈现不能与被摄体吸入同步。 通过呼吸引发的气味刺激范式，气味刺激的起始和持续时间矢量将在受试者之间变化。为了分析嗅觉fMRI数据，可以使用ONSET确定实际发作和持续时间矢量，并且可以使用这些向量在标准程序之后处理fMRI数据。 图4显示了响应于由开源软件SPM8（www.fil.ion.ucl.ac.uk/spm）处理的呼吸引发的气味刺激的样本脑激活图，其具有按照标准处理程序的实际气味发作和持续时间矢量。在双侧原发性嗅觉皮层中检测到显着的气味相关激活，右侧左侧皮质，右上肢/角回，左侧尾核和左侧中心/超上肢回（家系误差校正，p &lt;0.05，范围阈值= 6体素）。 <img alt="图1" class="xfigimg" src="/files/ftp_upload/54898/54898fig1.jpg" /> 图1 :实验设置示意图。放置在磁体室中的MRI兼容元件通过穿透板连接到容纳在控制室中的MRI控制台和嗅觉仪盒，在墙壁上分离有两个房间的波导。 <a href="http://ecsource.jove.com/files/ftp_upload/54898/54898fig1large.jpg" target="_blank">请点击此处查看此图的较大版本。</a> <img alt="图2" class="xfigimg" src="/files/ftp_upload/54898/54898fig2.jpg" /> 图2 <strong&gt;:气味传播范例的例证。 （a）固定时间范例，呼吸和异味递送之间频繁出现的同步问题导致固定时间范例中气味分布量的变化和发生。 （b）呼吸引发的范式倾向于在受试者之间产生更一致的结果。 <a href="http://ecsource.jove.com/files/ftp_upload/54898/54898fig2large.jpg" target="_blank">请点击此处查看此图的较大版本。</a> <img alt="图3" class="xfigimg" src="/files/ftp_upload/54898/54898fig3.jpg" /> 图3 :样本呼吸图。 （a）呼吸传感器未正确设置时的示例呼吸痕迹;呼吸模式高原变得不规则。 （b）用正确放置的呼吸传感器记录的代表性常规呼吸模式;在这种情况下，配给模式与水平峰值一致，并且气味输送可以与吸入同步。 <a href="http://ecsource.jove.com/files/ftp_upload/54898/54898fig3large.jpg" target="_blank">请点击此处查看此图的较大版本。</a> <img alt="图4" class="xfigimg" src="/files/ftp_upload/54898/54898fig4.jpg" /> 图4 : 样本大脑激活图。一个健康的受试者响应呼吸引发的薰衣草气味模拟（家庭误差校正，p &lt;0.05，范围阈值= 6体素）。显着的激活包括右主要嗅皮层（POC，MNI坐标x = 20，y = 6，z = -14），左POC（x = -22，y = 4，z = -10） 46，y = 20，z = -10），右超脉络膜/角回（x = 66，y = -48，z = 28），左尾状核（x = -14，y = 6，z = 10）并离开中央/超级市场回（x = -66，y = -24，z = 20）。 <a href="http://ecsource.jove.com/files/ftp_upload/54898/54898fig4large.jpg" target="_blank">请点击此处查看此图的较大版本。</a> <table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always"><tbody><tr><td> 添味剂 </td><td> 闻起来像 </td><td> 复合 </td><td> 三叉神经刺激 </td><td> 溶剂 </td></tr><tr><td>乙醛29 </td><td>绿色，甜蜜</td><td>简单</td><td>没有</td><td>水</td></tr><tr><td>氨29 </td><td>辛辣，清洁</td><td>简单</td><td>是</td><td>水</td></tr><tr><td>乙酸戊酯30 </td><td>香蕉，苹果</td><td>简单</td><td>一些</td><td>水</td></tr><tr><td>正丁醇31,32 </td><td>轻度酒精</TD&gt; <td>简单</td><td>没有</td><td>水</td></tr><tr><td>乙酸正丁酯31 </td><td>甜蜜和果香</td><td>简单</td><td>是</td><td>水</td></tr><tr><td>丁酸33 </td><td>酸，腐臭</td><td>简单</td><td>是</td><td>水</td></tr><tr><td> Citral 30,33 </td><td>柠檬</td><td>简单</td><td>一些</td><td>水</td></tr><tr><td>二氧化碳34,35 </td><td>无臭的</td><td>简单</td><td>是</td><td> N / A </td></tr><tr><td>丁酸乙酯30 </td><td>菠萝</td><td>简单</td><td>是</td><td>水</td></tr><tr><td>桉树脑35 </td><td>桉树</td><td>简单</td><td>是</td><td>乙醇</td></tr><tr><td>丁香酚33,36 </td><td>丁香，辣</td><td>简单</td><td>没有</td><td>乙醇</td></tr><tr><td>香叶醇<sup&gt; 33 </td><td>甜玫瑰，花香</td><td>简单</td><td>没有</td><td>乙醇</td></tr><tr><td>硫酸34,36 </td><td>臭鸡蛋</td><td>简单</td><td>没有</td><td>水</td></tr><tr><td>薰衣草24,37 </td><td>薰衣草</td><td>复杂</td><td>没有</td><td>乙醇</td></tr><tr><td>薄荷醇33 </td><td>薄荷</td><td>简单</td><td>是</td><td>乙醇</td></tr><tr><td>水杨酸甲酯33 </td><td>冬青薄荷</td><td>简单</td><td>是</td><td>乙醇</td></tr><tr><td>广藿香38 </td><td>湿土</td><td>复杂</td><td>是</td><td>乙醇</td></tr><tr><td> 1-丙醇31 </td><td>摩擦酒精</td><td>简单</td><td>是</td><td>乙醇</td></tr><tr><td> 苯乙醇36,39 </td><td>玫瑰</td><td>简单</td><td> ñØ </td><td>乙醇</td></tr><tr><td>迷迭香油38 </td><td>迷迭香</td><td>复杂</td><td>是</td><td>乙醇</td></tr><tr><td>二氧化硫29 </td><td>刺激，刺鼻</td><td>简单</td><td>是</td><td>水</td></tr><tr><td>戊酸33 </td><td> Rancid奶酪</td><td>简单</td><td>是</td><td>水</td></tr><tr><td>香草醛29 </td><td>香草</td><td>简单</td><td>没有</td><td>乙醇</td></tr><tr><td> Ylang Ylang 38 </td><td>花香水</td><td>复杂</td><td>是</td><td>乙醇</td></tr><tr><td colspan="5"> ***参见手稿末尾</td></tr></tbody></table> 表1:嗅觉功能磁共振成像研究中使用的常用气味剂 。

Watch this Scientific Journal Video about A Free-breathing fMRI Method to Study Human Olfactory Function at JoVE.com

A Free-breathing fMRI Method to Study Human Olfactory Function

我们介绍从人类中心嗅觉系统获得可靠的功能磁共振成像（fMRI）数据的技术挑战和解决方案。这包括嗅觉fMRI范式设计中的特殊考虑，使用MRI兼容嗅觉仪的fMRI数据采集描述，气味选择以及用于数据后处理的专用软件工具。

一种免费呼吸功能磁共振成像方法研究人类嗅觉功能

The study of human olfaction is a highly complex and valuable field with applications ranging from biomedical research to clinical evaluation. Currently, ...

a-free-breathing-fmri-method-to-study-human-olfactory-function

Nanyang Technological University

Research

JoVE Journal

Neuroscience

9.6K 次观看.  Pennsylvania State University College of Medicine. 我们介绍从人类中心嗅觉系统获得可靠的功能磁共振成像（fMRI）数据的技术挑战和解决方案。这包括嗅觉fMRI范式设计中的特殊考虑，使用MRI兼容嗅觉仪的fMRI数据采集描述，气味选择以及用于数据后处理的专用软件工具。 

视频: A Free-breathing fMRI Method to Study Human Olfactory Function

Combining Transcranial Magnetic Stimulation and fMRI to Examine the Default Mode Network

The default mode network is a group of brain regions that are active when an individual is not focused on the outside world and the brain is at "wakeful rest."1,2,3 It is thought the default mode network corresponds to self-referential or "internal mentation".2,3
It has been hypothesized that, in humans, activity within the default mode network is correlated with certain pathologies (for instance, hyper-activation has been linked to schizophrenia 4,5,6 and autism spectrum disorders 7 whilst hypo-activation of the network has been linked to Alzheimer's and other neurodegenerative diseases 8). As such, noninvasive modulation of this network may represent a potential therapeutic intervention for a number of neurological and psychiatric pathologies linked to abnormal network activation. One possible tool to effect this modulation is Transcranial Magnetic Stimulation: a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate cortical excitability (either increasing or decreasing it) via the application of localized magnetic field pulses.9
In order to explore the default mode network's propensity towards and tolerance of modulation, we will be combining TMS (to the left inferior parietal lobe) with functional magnetic resonance imaging (fMRI). Through this article, we will examine the protocol and considerations necessary to successfully combine these two neuroscientific tools.

In this article, we examine the methodology and considerations relevant to the combination of TMS and fMRI to examine the effects of brain stimulation on the default network.

结合经颅磁刺激和功能磁共振成像检查默认模式网络

The default mode network is a group of brain regions that are active when an individual is not focused on the outside world and the brain is at "wakeful ...

科研

神经科学

Simple and Computer-assisted Olfactory Testing for Mice

Olfaction is highly conserved among species and is required for reproduction and survival.
In humans, olfaction is also one of the senses that is affected with aging and is a strong predictor of neurodegenerative diseases. Thus, olfaction testing is used as a non-invasive diagnostic method to detect neurological deficits early on. In order to understand the mechanisms underlying olfactory network susceptibility, olfactory research in rodents has gained momentum in the past decade.
Here, we present a very simple, time efficient and reproducible olfactory testing method of innate odor perception and sensitivity in mice without the need of any prior food or water restriction. The tests are performed in a familiar environment to the mice, require only the scents and a 2 min session of odorant exposure. The analysis is performed, post-hoc, using computer-assisted commands on ImageJ and can be, therefore, carried out from start to end by one researcher.
This protocol does not require any special hardware or setup and is indicated for any laboratory interested in testing olfactory perception and sensitivity.

We present a simple and unbiased olfactory test in mice. With this protocol olfactory discrimination, preference, avoidance and sensitivity to a novel odor as compared to water can be assessed in single behavioral sessions. This method is indicated for a single experimenter and analysis is based on computer-assisted video processing.

简单和计算机辅助测试嗅觉的小鼠

Olfaction is highly conserved among species and is required for reproduction and survival.
In humans, olfaction is also one of the senses that is affected ...

行为学

Lentivirus-mediated Genetic Manipulation and Visualization of Olfactory Sensory Neurons in vivo

Development of a precise olfactory circuit relies on accurate projection of olfactory sensory neuron (OSN) axons to their synaptic 
targets in the olfactory bulb (OB). The molecular mechanisms of OSN axon growth and targeting are not well understood. Manipulating gene expression and subsequent 
visualizing of single OSN axons and their terminal arbor morphology have thus far been challenging. To study gene function at the single cell level within a specified 
time frame, we developed a lentiviral based technique to manipulate gene expression in OSNs in vivo. Lentiviral particles are delivered to OSNs by microinjection 
into the olfactory epithelium (OE). Expression cassettes are then permanently integrated into the genome of transduced OSNs. Green fluorescent protein expression 
identifies infected OSNs and outlines their entire morphology, including the axon terminal arbor. Due to the short turnaround time between microinjection and 
reporter detection, gene function studies can be focused within a very narrow period of development. With this method, we have detected GFP expression within as 
few as three days and as long as three months following injection. We have achieved both over-expression and shRNA mediated knock-down by lentiviral microinjection. 
This method provides detailed morphologies of OSN cell bodies and axons at the single cell level in vivo, and thus allows characterization of candidate gene function 
during olfactory development.

Lentivirus-mediated Genetic Manipulation and Visualization of Olfactory Sensory Neurons in vivo

We present a lentiviral technique for genetic manipulation and visualization of single olfactory sensory neuron axon and its terminal arborization in vivo.

嗅觉感官神经元的慢病毒介导的遗传操作和可视化在体内</em

Development of a precise olfactory circuit relies on accurate projection of olfactory sensory neuron (OSN) axons to their synaptic 
targets in the ...

Correlating Behavioral Responses to fMRI Signals from Human Prefrontal Cortex: Examining Cognitive Processes Using Task Analysis

The aim of this methods paper is to describe how to implement a neuroimaging technique to examine complementary brain processes engaged by two similar tasks. Participants' behavior during task performance in an fMRI scanner can then be correlated to the brain activity using the blood-oxygen-level-dependent signal. We measure behavior to be able to sort correct trials, where the subject performed the task correctly and then be able to examine the brain signals related to correct performance. Conversely, if subjects do not perform the task correctly, and these trials are included in the same analysis with the correct trials we would introduce trials that were not only for correct performance. Thus, in many cases these errors can be used themselves to then correlate brain activity to them. We describe two complementary tasks that are used in our lab to examine the brain during suppression of an automatic responses: the stroop1 and anti-saccade tasks. The emotional stroop paradigm instructs participants to either report the superimposed emotional 'word' across the affective faces or the facial 'expressions' of the face stimuli1,2. When the word and the facial expression refer to different emotions, a conflict between what must be said and what is automatically read occurs. The participant has to resolve the conflict between two simultaneously competing processes of word reading and facial expression. Our urge to read out a word leads to strong 'stimulus-response (SR)' associations; hence inhibiting these strong SR's is difficult and participants are prone to making errors. Overcoming this conflict and directing attention away from the face or the word requires the subject to inhibit bottom up processes which typically directs attention to the more salient stimulus. Similarly, in the anti-saccade task3,4,5,6, where an instruction cue is used to direct only attention to a peripheral stimulus location but then the eye movement is made to the mirror opposite position. Yet again we measure behavior by recording the eye movements of participants which allows for the sorting of the behavioral responses into correct and error trials7 which then can be correlated to brain activity. Neuroimaging now allows researchers to measure different behaviors of correct and error trials that are indicative of different cognitive processes and pinpoint the different neural networks involved.

The goal of our research is to correlate behavior to brain activity. Accurate behavioral measures and imaging techniques allow us to elucidate brain-behavior relationships.

关联从人类前额叶皮层的fMRI信号的行为反应：检查的认知过程，使用任务分析

The aim of this methods paper is to describe how to implement a neuroimaging technique to examine complementary brain processes engaged by two similar ...

Imaging Odor-Evoked Activities in the Mouse Olfactory Bulb using Optical Reflectance and Autofluorescence Signals

In the brain, sensory stimulation activates distributed populations of neurons among functional modules which participate to the coding of the stimulus. Functional optical imaging techniques are advantageous to visualize the activation of these modules in sensory cortices with high spatial resolution. In this context, endogenous optical signals that arise from molecular mechanisms linked to neuroenergetics are valuable sources of contrast to record spatial maps of sensory stimuli over wide fields in the rodent brain.
Here, we present two techniques based on changes of endogenous optical properties of the brain tissue during activation. First the intrinsic optical signals (IOS) are produced by a local alteration in red light reflectance due to: (i) absorption by changes in blood oxygenation level and blood volume (ii) photon scattering. The use of in vivo IOS to record spatial maps started in the mid 1980's with the observation of optical maps of whisker barrels in the rat and the orientation columns in the cat visual cortex1. IOS imaging of the surface of the rodent main olfactory bulb (OB) in response to odorants was later demonstrated by Larry Katz's group2. The second approach relies on flavoprotein autofluorescence signals (FAS) due to changes in the redox state of these mitochondrial metabolic intermediates. More precisely, the technique is based on the green fluorescence due to oxidized state of flavoproteins when the tissue is excited with blue light. Although such signals were probably among the first fluorescent molecules recorded for the study of brain activity by the pioneer studies of Britton Chances and colleagues3, it was not until recently that they have been used for mapping of brain activation in vivo. FAS imaging was first applied to the somatosensory cortex in rodents in response to hindpaw stimulation by Katsuei Shibuki's group4.
The olfactory system is of central importance for the survival of the vast majority of living species because it allows efficient detection and identification of chemical substances in the environment (food, predators). The OB is the first relay of olfactory information processing in the brain. It receives afferent projections from the olfactory primary sensory neurons that detect volatile odorant molecules. Each sensory neuron expresses only one type of odorant receptor and neurons carrying the same type of receptor send their nerve processes to the same well-defined microregions of &tilde;100&mu;m3 constituted of discrete neuropil, the olfactory glomerulus (Fig. 1). In the last decade, IOS imaging has fostered the functional exploration of the OB5, 6, 7 which has become one of the most studied sensory structures. The mapping of OB activity with FAS imaging has not been performed yet.
Here, we show the successive steps of an efficient protocol for IOS and FAS imaging to map odor-evoked activities in the mouse OB.

This article presents the protocols of intrinsic optical signals and flavoproteins autofluorescence signals imaging to map odor-evoked activities at the surface of the olfactory bulb in mice.

在小鼠嗅球成像气味诱发的活动，利用光学反射和自体荧光信号

In the brain, sensory stimulation activates distributed populations of neurons among functional modules which participate to the coding of the stimulus. ...

Olfactory Context Dependent Memory: Direct Presentation of Odorants

Information is retrieved more effectively when the retrieval occurs in the same context as that in which the information was first encoded. This is termed context dependent memory (CDM). One category of cues that have been shown to effectively produce CDM effects are odors. However, it is unclear what the boundary conditions of these CDM effects are. In particular, given that olfaction has been called an implicit sense, it is possible that odors are only effective mnemonic cues when they are presented in the background. This assertion seems even more likely given that previous research has shown odors to be poor cues during paired associate memory tests, where odors are in the focus of attention as mnemonic cues for other information. In order to determine whether odors are only effective contextual mnemonic cues when presented outside the central focus of an observer, an olfactory CDM experiment was performed in which odorants were presented directly, rather than ambiently. Direct presentation was accomplished with the aid of an olfactometer. The olfactometer not only allows for direct presentation of odorants, but provides other methodological benefits, including the allowance of trial by trial manipulations of odorant presentations and, relatedly, time-specific releases of odorants. The presence of the same odor during both encoding and retrieval enhanced memory performance, regardless of whether the odor was presented ambiently or directly. This finding can serve as a basis for future olfactory CDM research which can utilize the benefits of direct presentation.

The use of an olfactometer for directly presenting odorants opens exciting opportunities for researchers of olfactory memory. The current paper discusses issues related to this methodology as related to a previously published experiment on olfactory context dependent memory.

嗅觉语境依赖性记忆: 气味的直接表现

Information is retrieved more effectively when the retrieval occurs in the same context as that in which the information was first encoded. This is termed ...

Training Dogs for Awake, Unrestrained Functional Magnetic Resonance Imaging

We present a canine functional Magnetic Resonance Imaging (fMRI) training protocol that can be done in a cost-effective manner, with high-energy dogs, for acquisition of functional and structural data. This method of training dogs for awake, unrestrained fMRI employs a generalization procedure of stationing in several dissimilar locations to facilitate transfer of the stationing behavior to the real MRI scan environment; it does so without the need for extensive training time in the MRI scan environment, which can be expensive. Further, this method splits the training of a stationing (i.e., chin rest) behavior from desensitization to the MRI environment (i.e., 100+ decibel scan audio), the latter accomplished during dedicated Auditory Exposure conditioning sessions. The complete training and testing protocol required 14 hours and resulted in immediate transfer to novel locations. We also present examples of canine fMRI data that have been acquired from visual face processing and olfactory discrimination paradigms.

Magnetic resonance imaging (MRI) on unrestrained awake dogs is a new method with several advantages over imaging with physical or chemical restraint. This protocol introduces a cost-effective training method that minimizes training in the MRI environment, which can be expensive, and maximizes the subject pool available for canine functional MRI.

训练犬为觉醒，无节制的功能磁共振成像

We present a canine functional Magnetic Resonance Imaging (fMRI) training protocol that can be done in a cost-effective manner, with high-energy dogs, for ...

<meta charset="utf8"></head><body>为啮齿动物嗅觉实验设计灵活、经济高效的嗅觉计

Constructing an Olfactometer for Rodent Olfactory Behavior Studies

The use of olfactometers to study rodent behavior and brain activity during olfactory tasks is crucial for understanding brain circuits. These sophisticated devices allow researchers to precisely control and deliver odor stimuli, enabling the investigation of complex olfactory processes in rodents. Although commercially available olfactometers are convenient, they present challenges when technical issues arise, often requiring costly assistance and potentially disrupting research timelines. This article details the construction of a custom olfactometer specifically designed for mouse olfactory behavior experiments, providing a comprehensive list of parts and step-by-step instructions. The olfactometer is controlled through MATLAB, offering a user-friendly interface for researchers. Importantly, the open-source code allows users to modify and adapt the system, tailoring behavioral tasks to meet specific experimental needs. Building a customized olfactometer empowers users with the knowledge and capability to perform custom experimental design and troubleshooting independently, saving both time and resources. This approach not only enhances research flexibility but also fosters a deeper understanding of the equipment's functionality, ultimately leading to more robust and reliable olfactory studies in rodents.

<meta charset="utf8"></head><body>构建嗅觉计用于啮齿动物嗅觉行为研究 近红外光谱 心理咨询中的超扫描研究

This protocol describes the construction of an olfactometer for go/no-go olfactory behavior experiments. Step-by-step instructions, along with images, are provided to ensure the successful construction of the olfactometer. Information for troubleshooting issues encountered during the process is also included.

一种免费呼吸功能磁共振成像方法研究人类嗅觉功能

摘要

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此视频中的章节

结合经颅磁刺激和功能磁共振成像检查默认模式网络

简单和计算机辅助测试嗅觉的小鼠

嗅觉感官神经元的慢病毒介导的遗传操作和可视化在体内

关联从人类前额叶皮层的fMRI信号的行为反应：检查的认知过程，使用任务分析

在小鼠嗅球成像气味诱发的活动，利用光学反射和自体荧光信号

嗅觉语境依赖性记忆: 气味的直接表现

训练犬为觉醒，无节制的功能磁共振成像

构建用于啮齿动物嗅觉行为研究的嗅觉计

构建用于啮齿动物嗅觉行为研究的嗅觉计

构建用于啮齿动物嗅觉行为研究的嗅觉计